This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. NTP-binding proteins, such as kinases and ATPases, are important effectors of biological activity in both prokaryotes and eukaryotes. Therefore, they are also important drug targets. In the following proposal we propose to perform structural studies on several key human NTP-binding proteins to further elucidate their mechanism of function, as well as to integrate these proteins into an interactive structure-based drug design cycle. Our goal is to perform structural studies on multiple projects. The structural results generated by these experiments will be used in an iterative structure-based drug design program aimed at developing therapeutics against very aggressive human cancers such as melanoma, breast cancer, and small-cell lung cancer. Rapid design and optimization of the lead compounds in such a drug design cycle is incumbent on timely access to synchrotron sources for the generation of the needed structural data.